US Hispanics underutilize medication treatment for major depressive disorder (MOD). The retention rate in antidepressant therapy (ADT) among Hispanics is half that of majority whites. Depressed Hispanics also find ADT less acceptable, are less likely to fill antidepressant prescriptions, and have lower medication adherence than the majority population, even after adjusting for demographic and clinical covariates. Three main causes of ADT underutilization -dissatisfaction with treatment, over-reliance on early treatment gains, and environmental obstacles- are magnified by cultural elements in the case of Hispanics. These elements include: concerns about potential stigmatization, dependence;and side effects due to ADT;expectations of medication use incompatible with antidepressants;and alternative constructions of the treatment and course of emotional illness. The resulting low cultural congruence of standard ADT leads many Hispanics to enter into this form of treatment with considerable uncertainty. This magnifies the adverse effect of existing environmental barriers leading to low retention and poor medication adherence. The public health consequences include higher MOD morbidity and recurrence, and rising healthcare costs. With NIMH support, our team developed a culturally adapted, novel intervention for improving Hispanic retention in ADT that can be conducted by a psychiatrist (stage I of intervention development). Called Motivational Antidepressant Therapy (MADT), this manualized method of pharmacotherapy delivery is based on Motivational Interviewing, a therapeutic approach to patient engagement that reduces ambivalence about participating in treatment. MADT has shown strong preliminary efficacy in facilitating retention and response of depressed Hispanics in the acute phase of MOD pharmacotherapy. The proposed stage II study would test the efficacy of MADT in an RCT against standard ADT in depressed Hispanics seeking outpatient psychiatric care at a research clinic. Retention, response, adherence, and patient satisfaction will be examined over 9 months of treatment. A mixed-method approach (quantitative- qualitative) will yield information on patient, intervention, and process of care characteristics affecting retention. If MADT is found to be more efficacious than standard ADT in this stage II trial, the mixed- method data will allow us to further develop MADT for a stage III effectiveness trial in community settings.